Serum concentration measurements in man of the radiosensitizer Ro-07-0582: some preliminary results

THE PROPERTIES of a clinically useful radiosensitizer of hypoxic and therefore radioresistant cells of solid tumours have been listed (Emmerson and HowardFlanders, 1965; Adams, 1973). Many of these criteria have been met in different drugs and recent progress has centred around a number of nitro-heterocyclic compounds (Chapman et al., 1972; Foster and Willson, 1973; Asquith et al., 1974b). The nitro-heterocyclic drug metronidazole (Flagyl, May and Baker) has been shown to increase the radiosensitivity of solid murine tumours (Begg, Sheldon and Foster, 1974; Rauth and Kaufman, 1975; Stone and Withers, 1974) and possesses favourable pharmacological and toxicological properties (see Asquith et al., 1974a for references) which have enabled the high drug doses required (about 200 mg/kg body weight) to be used in conjunction with radiotherapy in man (Urtasun et al., 1974; Deutsch et al., 1975). Metronidazole is a 5-nitroimidazole and there are theoretical reasons for expecting the analogous 2-nitroimidazoles to be more efficient radiosensitizers (Asquith et al., 1974b). Ro-07-0582 (1-(2nitro1 -imidazolyl)-3-methoxy-2-propanol, Roche Products Ltd) was selected for in vivo work on the basis of the results of in vitro testing of a number of 2-nitroimidazole compounds. Acceptecl 17 February 1975